The specific objectives of this contract are to develop and characterize a genetic model in the mouse, where the interaction of two mutant genes results in 100% of animals at birth showing a sacro-caudal spina bifida analogous to a common defect in man, and where homozygotes for one of those mutations are prenatally lethal with complete failure of neural tube closure. This research team will provide the animal model and relevant DNA probes to interested investigators. Recombinant DNA technology will be used to attempt to identify and clone the mutant genes in order to understand their mechanism of action. This study should provide an exceptional model for studies of NTDs in a mammal (murine). Heterozygous mutant mice with high incidence of NTDs should be produced with excellent genetic information available. By breeding and backcrossing, an outstanding opportunity exists for combining these genes with a genetic background that will intensify the magnitude of the NTD produced by modifier genes. Once the model is established it will be characterized genetically by identifying and cloning the mutant gene and provide gene probes potentially useful in the diagnosis of similar genetic factors in man.